Structural basis of actin sequestration by thymosin-β4

Implications for WH2 proteins

Edward Irobi, Adeleke H. Aguda, Mårten Larsson, Christophe Guerin, Helen L. Yin, Leslie D. Burtnick, Laurent Blanchoin, Robert C. Robinson

Research output: Contribution to journalArticle

89 Citations (Scopus)

Abstract

The WH2 (Wiscott-Aldridge syndrome protein homology domain 2) repeat is an actin interacting motif found in monomer sequestering and filament assembly proteins. We have stabilized the prototypical WH2 family member, thympsin-β4 (Tβ4), with respect to actin, by creating a hybrid between gelsolin domain 1 and the C-terminal half of Tβ4 (G1-Tβ4). This hybrid protein sequesters actin monomers, severs actin filaments and acts as a leaky barbed end cap. Here, we present the structure of the G1-Tβ4:actin complex at 2 Å resolution. The structure reveals that Tβ4 sequesters by capping both ends of the actin monomer, and that exchange of actin between Tβ4 and profilin is mediated by a minor overlap in binding sites. The structure implies that multiple WH2 motif-containing proteins will associate longitudinally with actin filaments. Finally, we discuss the role of the WH2 motif in arp2/3 activation.

Original languageEnglish (US)
Pages (from-to)3599-3608
Number of pages10
JournalEMBO Journal
Volume23
Issue number18
DOIs
StatePublished - Sep 15 2004

Fingerprint

Thymosin
Actins
Proteins
Actin Cytoskeleton
Monomers
Profilins
Gelsolin
Amino Acid Motifs
Binding Sites
Chemical activation

Keywords

  • Protein crystallography
  • SCAR
  • VCA
  • WASp
  • WH2

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Irobi, E., Aguda, A. H., Larsson, M., Guerin, C., Yin, H. L., Burtnick, L. D., ... Robinson, R. C. (2004). Structural basis of actin sequestration by thymosin-β4: Implications for WH2 proteins. EMBO Journal, 23(18), 3599-3608. https://doi.org/10.1038/sj.emboj.7600372

Structural basis of actin sequestration by thymosin-β4 : Implications for WH2 proteins. / Irobi, Edward; Aguda, Adeleke H.; Larsson, Mårten; Guerin, Christophe; Yin, Helen L.; Burtnick, Leslie D.; Blanchoin, Laurent; Robinson, Robert C.

In: EMBO Journal, Vol. 23, No. 18, 15.09.2004, p. 3599-3608.

Research output: Contribution to journalArticle

Irobi, E, Aguda, AH, Larsson, M, Guerin, C, Yin, HL, Burtnick, LD, Blanchoin, L & Robinson, RC 2004, 'Structural basis of actin sequestration by thymosin-β4: Implications for WH2 proteins', EMBO Journal, vol. 23, no. 18, pp. 3599-3608. https://doi.org/10.1038/sj.emboj.7600372
Irobi, Edward ; Aguda, Adeleke H. ; Larsson, Mårten ; Guerin, Christophe ; Yin, Helen L. ; Burtnick, Leslie D. ; Blanchoin, Laurent ; Robinson, Robert C. / Structural basis of actin sequestration by thymosin-β4 : Implications for WH2 proteins. In: EMBO Journal. 2004 ; Vol. 23, No. 18. pp. 3599-3608.
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